Reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that this prior art forms part of the common general knowledge in Malaysia or any other countries.
Angiogenesis relates to the formation or sprouting of new blood vessels from preexisting vessels. Under normal circumstances, angiogenesis is observed as the formation of blood vessels during, but not limiting to, wound healing and embryonal development. For the past few years, great efforts have been expended by researchers to understanding the regulation of angiogenesis, identifying pathways to angiogenesis and much has been written about the mechanisms as well as its pathologic and physiologic conditions. There are three major processes or stages involved in the formation of blood vessels; whereby the first stage is angiogenic activation of endothelial cells and degradation of basement membrane, the second stage is endothelial proliferation and migration, and the third stage is new vessel formation.
Stages of maturation and stabilization of the newly formed blood vessels occur by means of recruitment of pericytes which may involve angiogenic factors such as vascular endothelial growth factor (VEGF). Accordingly, vascular endothelial growth factor (VEGF) plays a major role in all these three main stages. It facilitates in inducing angiogenic activated state of endothelial cells for the blood vessel, proliferation and migration of stimulus from the preexisting blood vessel and expression of integrins in new vessel formation.
One of the major causes of human blindness or adult vision loss is age-related maculopathy, especially in industrialized countries. Generally, such cause is associated to interference of normal physiological process of angiogenesis as described earlier, particularly due to local expansion of blood vessels, or uncontrolled angiogenesis.
An example of a leading cause of adult vision loss is age-related macular degeneration (AMD). Recent studies have demonstrated that AMD is caused by an assortment of clinically ocular findings that leads to vision impairment and blindness. Generally, AMD occurs in two forms, dry and wet. In wet AMD, choroidal vessels pathologically grow through the retinal pigmented epithelial (RPE) cell layer into the subretinal space, a process known as choroidal neovascularization (CNV). According to scientific reports, CNV and ensuing leakage damage to the RPE and retinal cells would lead to permanent vision loss.
Because VEGF is an important biomarker in angiogenesis (Zahir K Otrock, 2010) in many cases, VEGF has been identified as the key molecule responsible for the growth and leakiness of CNV, and the primary regulatory factor of neovascularization of angiogenic diseases. It can be concluded that VEGF, is one of the most significant factors affecting endothelial cell (EC) proliferation, among others, its motility and vascular permeability.
Macrophages are a major source of VEGF and tumor necrosis factor (TNF)-□, thereby it is implicated in the pathogenesis of AMD due to their spatiotemporal distribution in the proximity of the CNV lesions particularly in experimental models and humans.
In US 2007203211 A1, there is disclosed a drug for use in preventing or treating angiogenic eye diseases, in which the method involves administering to a mammal in need thereof pharmaceutically effective amount of angiotensin II receptor antagonist. It is further disclosed that angiotensin II receptor antagonist is highly effective in the prevention or treatment of intraocular angiogenic diseases such as proliferative retinopathy or retinal vein occlusion. There is no explicit disclosure on using plant based materials as VEGF inhibitors.
A great majority of treatments and medications are chemical based or surgical based treatments which may not be favorable for patients at advanced ages. Further, it has been shown that treatment for AMD is effective for only a small proportion of patients, particularly patients who have well-defined choroidal neovascular membrane (CNVM) (Bressler et al, 2004).
Therefore, there is a need to identify a solution and effective treatment for ocular angiogenesis and thus inhibits human blindness derived from highly abundant sources, such as plant based materials.
It is primary object of the present invention to provide a composition and method thereof for use in the prevention and inhibition of vision loss due to angiogenesis associated diseases.
Still other objects of the present invention will become readily apparent to those skilled in the art from the following detailed description.